Current Issue : April-June Volume : 2022 Issue Number : 2 Articles : 5 Articles
Diabetes mellitus is characterized by chronic hyperglycemia that promotes ROS formation, causing severe oxidative stress. Furthermore, prolonged hyperglycemia leads to glycation reactions with formation of AGEs that contribute to a chronic inflammatory state. This research aims to evaluate the inhibitory activity of a-mangostin and four synthetic xanthenone derivatives against glycation and oxidative processes and on a-glucosidase, an intestinal hydrolase that catalyzes the cleavage of oligosaccharides into glucose molecules, promoting the postprandial glycemic peak. Antiglycation activity was evaluated using the BSA assay, while antioxidant capacity was detected with the ORAC assay. The inhibition of a-glucosidase activity was studied with multispectroscopic methods along with inhibitory kinetic analysis. a-Mangostin and synthetic compounds at 25 aM reduced the production of AGEs, whereas the a-glucosidase activity was inhibited only by the natural compound. a-Mangostin decreased enzymatic activity in a concentration-dependent manner in the micromolar range by a reversible mixed-type antagonism. Circular dichroism revealed a rearrangement of the secondary structure of a-glucosidase with an increase in the contents of a-helix and random coils and a decrease in a-sheet and a-turn components. The data highlighted the anti-a-glucosidase activity of a-mangostin together with its protective effects on protein glycation and oxidation damage....
A series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII and XIII). The imidazole ring of HST was replaced with different 5-membered heterocycles and the length of the aliphatic chain was varied. For the most interesting compounds some modifications on the terminal amino group were also performed. The most sensitive isoform to activation was hCA I (KA values in the low micromolar range), but surprisingly none of the new compounds displayed activity on hCA II. Some derivatives (1, 3a and 22) displayed an interesting selectivity for activating hCA I over hCA II, Va, VII and XIII....
A series of 5-methyl-7-phenyl-3H-thiazolo[4,5-b]pyridin-2-ones has been designed, synthesized, and characterized by spectral data. Target compounds were screened for their antimicrobial activity against some pathogenic bacteria and fungi, and most of them showed moderate activity, especially compound 3g, which displayed the potent inhibitory effect against Pseudomonas aeruginosa and Escherichia coli with MIC value of 0.21 μM. The active thiazolopyridine derivatives 3c, 3f, and 3g were screened for their cytotoxicity effects on HaCat, Balb/c 3T3 cells using MTT assay, which revealed promising results. In silico assessment for compounds 3c, 3f, and 3g also revealed suitable drug-like parameters and ADME properties. The binding interactions of the most active compound 3g were performed through molecular docking against MurD and DNA gyrase, with binding energies and an inhibitory constant compared to the reference drug ciprofloxacin. The tested thiazolo[4,5-b]pyridines constitute an exciting background for the further development of new synthetic antimicrobial agents....
The global health concern of antimicrobial resistance has harnessed research interest to find newclasses of antibiotics to combat disease-causing pathogens. In our studies, 3-halobenzo[b]thiophene derivatives were synthesized and tested for their antimicrobial activities using the broth microdilution susceptibility method. The 3-halo substituted benzo[b]thiophenes were synthesized starting from 2-alkynyl thioanisoles using a convenient electrophilic cyclization methodology that utilizes sodium halides as the source of electrophilic halogens when reacted along with copper(II) sulfate. This environmentally benign methodology is facile, uses ethanol as the solvent, and results in 3-halo substituted benzo[b]thiophene structures in very high yields. The cyclohexanol-substituted 3-chloro and 3-bromobenzo[b]thiophenes resulted in a low MIC of 16 g/mL against Gram-positive bacteria and yeast. Additionally, in silico absorption, distribution, metabolism, and excretion (ADME) properties of the compounds were determined. The compounds with the lowest MIC values showed excellent drug-like properties with no violations to Lipinski, Veber, and Muegge filters. The time-kill curve was obtained for cyclohexanol-substituted 3-chlorobenzo[b]thiophenes against Staphylococcus aureus, which showed fast bactericidal activity at MIC....
A series of (S)-3-(1-aminoethyl)-8-pyrimidinyl-2-phenylisoquinoline-1(2H)-ones 3a–k was synthesized in 40–98% yield through Suzuki–Miyaura coupling using Pd(PPh3)2Cl2, Sphos, and K2CO3 in THF/H2O mixed solvent. All newly synthesized compounds were evaluated for cell viability (IC50) against MDA-MB-231, HeLa, and HepG2 cells. The antitumor activities of 3a–k were improved when various pyrimidine motifs were introduced at position C-8 of the isoquinolinone ring....
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